Indigenous microbiota protects development of medication-related osteonecrosis induced by periapical disease in mice.
10.1038/s41368-022-00166-4
- Author:
Wen DU
1
;
Mengyu YANG
2
;
Terresa KIM
2
;
Sol KIM
2
;
Drake W WILLIAMS
2
;
Maryam ESMAEILI
2
;
Christine HONG
3
;
Ki-Hyuk SHIN
2
;
Mo K KANG
2
;
No-Hee PARK
2
;
Reuben H KIM
4
Author Information
1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
2. The Shapiro Family Laboratory of Viral Oncology and Aging Research, Los Angeles, USA.
3. Department of Orofacial Sciences, UCSF School of Dentistry, San Francisco, USA.
4. The Shapiro Family Laboratory of Viral Oncology and Aging Research, Los Angeles, USA. rkim@dentistry.ucla.edu.
- Publication Type:Journal Article
- MeSH:
Animals;
Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control*;
Bone Density Conservation Agents;
Diphosphonates;
Female;
Humans;
Mice;
Microbiota;
Periapical Diseases;
Zoledronic Acid
- From:
International Journal of Oral Science
2022;14(1):16-16
- CountryChina
- Language:English
-
Abstract:
Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.
